Bottom Line:
The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio.Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

Objectives: Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity.

Materials and methods: Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively.

Results: The cytotoxic effects of different concentration of VPA on MCF-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).

Conclusion: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

Figure 1: Valproic acid (VPA) cytotoxic effects (means±SD) on MCF-7 breast cancer cells. One-way ANOVA followed by post-hoc Tucky’s test was used to compare the mean Cell Viability (%) among different concentrations of VPA at 24, 48 and 72 hr (*P<0.05 and **P<0.005 compared to the control for 24, 48 and 72 hr, respectively)

Mentions:
To determine the effects of VPA on MCF-7, cells were exposed to various concentrations of VPA (0-32 mM) for 24, 48 and 72 hr. Assessment of cell viability by neutral red test showed that with increasing dose and treatment time, an increase in cytotoxic effects was observed and the concentrations of 8, 16 and 32 mM had the greatest effects compared with control (P<0.05). Also, LC50 value for VPA in MCF-7 cells after 48 and 72 hr were about 12 and 7 mM, respectively (Figure 1).

Figure 1: Valproic acid (VPA) cytotoxic effects (means±SD) on MCF-7 breast cancer cells. One-way ANOVA followed by post-hoc Tucky’s test was used to compare the mean Cell Viability (%) among different concentrations of VPA at 24, 48 and 72 hr (*P<0.05 and **P<0.005 compared to the control for 24, 48 and 72 hr, respectively)

Mentions:
To determine the effects of VPA on MCF-7, cells were exposed to various concentrations of VPA (0-32 mM) for 24, 48 and 72 hr. Assessment of cell viability by neutral red test showed that with increasing dose and treatment time, an increase in cytotoxic effects was observed and the concentrations of 8, 16 and 32 mM had the greatest effects compared with control (P<0.05). Also, LC50 value for VPA in MCF-7 cells after 48 and 72 hr were about 12 and 7 mM, respectively (Figure 1).

Bottom Line:
The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio.Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.

Objectives: Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity.

Materials and methods: Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively.

Results: The cytotoxic effects of different concentration of VPA on MCF-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001).

Conclusion: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti-cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis.